and configurational isomers, mixtures of enantiomers such as racemates, diastereomers, mixtures of diastereomers, diastereomeric racemates, and mixtures of diastereomeric racemates, as well as pharmaceutically acceptable salts, solvent complexes, and morphological forms.

22. Thiophene derivatives according to claim 21 wherein A represents -CH=CH-, and R1, R2, R3, and X are as defined in claim 21.

23. Thiophene derivatives according to claim 21 wherein A represents -NH-CH2-, and R1, R2, R3, and X are as defined in claim 21.

24. Thiophene derivatives accoding to claim 21 wherein A represents -CH2CH2-, and R1, R2, R3, and X are as defined in claim 21.

25. Thiophene derivatives according to claim 21 wherein X represents N, and R1, R2, R3, and A are as defined in claim 21. 26. Thiophene derivatives according to claim 21 wherein X represents C-R4, and R1, R2, R3, R4, and A are as defined in claim 21.

62. A thiophene derivative according to any of claims 1 to 61 for use as a medicament.

63. A process for the manufacture of compounds as claimed in any one of claims 1 to 61 , which process comprises

a) reacting the compound of Structure 9 or 10 with 2-mercaptoacetic acid in the presence of a base;

Structure 9 Structure 10

b) reacting a compound of Structure 8 with an non-aqueous base;

Structure 8

c) reacting a compound of Structure 7 with an aqueous base; Structure 7

d) reacting a compound of Structure 1 with a compound of Structure 2 in the presence of activating agents,

Structure 2

e) reacting a compound of Structure 1 with N,O-dimethyIhydroxylamine in the presence of an activating agent;

f) reacting a compound of Structure 3 with a Grignard reagent of Structure 4;

Structure 4

g) reacting a compound of Structure 1 with methyllithium;

h) reacting a compound of Structure 5 with a compound of Structure 6 in the presence of a base; Structure 5 Structure 6

i) reacting a compound of Structure 11 with hydrogen in the presence of a hydrogenation catalyst.

64. Pharmaceutical compositions containing a compound according to any of claims 1 to 61 and usual carrier materials and adjuvants for the prevention or treatment of disorders associated with an activated immune system.

65. Pharmaceutical compositions containing a compound according to any of claims 1 to 61 and usual carrier materials and adjuvants for the prevention or treatment of organ transplant rejection or graft-versus-host diseases.

67. Pharmaceutical compositions according to claim 66, for the treatment of prevention of disorders which are selected from the group consisting of autoimmune syndromes including rheumatoid arthritis, multiple sclerosis, myasthenia gravis; pollen allergies; type I diabetes; prevention of psoriasis; Crohn’s disease; post-infectious autoimmune diseases including rheumatic fever and post-infectious glomerulonephritis; and metastasis of carcinoma.

68. Use of one or more compounds of the General Formula (I) in claim 1 for the prevention or treatment of diseases or disorders associated with an activated immune system.

69. Use of one or more compounds of the General Formula (II) in claim 21 for the prevention or treatment of diseases or disorders associated with an activated immune system.

70. Use of one or more compounds of the General Formula (III) in claim 41 for the prevention or treatment of diseases or disorders associated with an activated immune system. 71. Use of one or more compounds of the General Formula (I) in claim 1 for the prevention or treatment of organ transplant rejection or graft-versus-host diseases.

72. Use of one or more compounds of the General Formula (II) in claim 21 for the prevention or treatment of organ transplant rejection or graft-versus-host diseases.

73. Use of one or more compounds of the General Formula (III) in claim 41 for the prevention or treatment of organ transplant rejection or graft-versus-host diseases.

78. Use of one or more compounds of General Formula (II) according to claim 69 in which said disorders are selected from the group consisting of autoimmune syndromes including rheumatoid arthritis, multiple sclerosis, myasthenia gravis; pollen allergies; type I diabetes; prevention of psoriasis; Crohn’s disease; post¬ infectious autoimmune diseases including rheumatic fever and post-infectious glomerulonephritis; and metastasis of carcinoma.

79. Use of one or more compounds of General Formula (III) according to claim 70 in which said disorders are selected from the group consisting of autoimmune syndromes including rheumatoid arthritis, multiple sclerosis, myasthenia gravis; pollen allergies; type I diabetes; prevention of psoriasis; Crohn’s disease; post¬ infectious autoimmune diseases including rheumatic fever and post-infectious glomerulonephritis; and metastasis of carcinoma.

80. Use of one or more compounds of the General Formula (I) in claim 1 in combination with one or several immunosuppressant compounds for the treatment of disorders associated with an activated immune system.

81. Use of one or more compounds of the General Formula (II) in claim 21 in combination with one or several immunosuppressant compounds for the treatment of disorders associated with an activated immune system.

82. Use of one or more compounds of the General Formula (III) in claim 41 in combination with one or several immunosuppressant compounds for the treatment of disorders associated with an activated immune system.

83. Use of one or more compounds of General Formula (I) according to claim 80 wherein said other immunosuppressant compound is selected from the group consisting of cyclosporin, daclizumab, basiliximab, everolimus, tacrolimus (FK506), azathiopirene, leflunomide, 15-deoxysperguaIin, or other immunosuppressant drugs.

84. Use of one or more compounds of General Formula (II) according to claim 81 wherein said other immunosuppressant compound is selected from the group consisting of cyclosporin, daclizumab, basiliximab, everolimus, tacrolimus (FK506), azathiopirene, leflunomide, 15-deoxyspergualin, or other immunosuppressant drugs.

85. Use of one or more compounds of General Formula (III) according to claim 82 wherein said other immunosuppressant compound is selected from the group consisting of cyclosporin, daclizumab, basiliximab, everolimus, tacrolimus (FK506), azathiopirene, leflunomide, 15-deoxyspergualin, or other immunosuppressant drugs.

86. A method for the prevention or treatment of disorders associated with an activated immune system comprising the administration to the patient of a pharmaceutical composition containing at least one compound of the General Formula (I) in claim 1.

87. A method for the prevention or treatment of disorders associated with an activated immune system comprising the administration to the patient of a pharmaceutical composition containing at least one compound of the General Formula (II) in claim 21.

88. A method for the prevention or treatment of disorders associated with an activated immune system comprising the administration to the patient of a pharmaceutical composition containing at least one compound of the General Formula (III) in claim 41. 89. A method for the prevention or treatment of disorders of organ transplant rejection or graft-versus-host diseases comprising the administration to the patient of a pharmaceutical composition containing at least one compound of the General Formula (I) in claim 1.

90. A method for the prevention or treatment of disorders of organ transplant rejection or graft-versus-host diseases comprising the administration to the patient of a pharmaceutical composition containing at least one compound of the General Formula (II) in claim 21.

91. A method for the prevention or treatment of disorders of organ transplant rejection or graft-versus-host diseases comprising the administration to the patient of a pharmaceutical composition containing at least one compound of the General Formula (III) in claim 41.

92. A method according to claim 86 or 89 by administering to a patient a dose of the thiophene derivative of the General Formula (I) in claim 1 between 0.5 mg and 1000 mg per day.

93. A method according to claim 87 or 90 by administering to a patient a dose of the thiophene derivative of the General Formula (II) in claim 21 between 0.5 mg and 1000 mg per day.

94. A method according to claim 88 or 91 by administering to a patient a dose of the thiophene derivative of the General Formula (III) in claim 41 between 0.5 mg and 1000 mg per day.

95. A method according to claim 92 by administering to a patient a dose of the thiophene derivative of the General Formula (I) between 1 mg and 500 mg per day. 96. A method according to claim 93 by administering to a patient a dose of the thiophene derivative of the General Formula (II) between 1 mg and 500 mg per day.

97. A method according to claim 94 by administering to a patient a dose of the thiophene derivative of the General Formula (III) between 1 mg and 500 mg per day.

98. A method according to claim 92 by administering to a patient a dose of the thiophene derivative of the General Formula (I) between 5 mg and 200 mg per day.

99. A method according to claim 93 by administering to a patient a dose of the thiophene derivative of the General Formula (II) between 5 mg and 200 mg per day.

100. A method according to claim 94 by administering to a patient a dose of the thiophene derivative of the General Formula (III) between 5 mg and 200 mg per day.

101. A process for the preparation of a pharmaceutical composition comprising a compound of the General Formula (I) in claim 1, characterized by mixing one or more active ingredients according to any one of claims 1 to 20, and 61 with inert excipients in a manner known per se.

102. A process for the preparation of a pharmaceutical composition comprising a compound of the General Formula (II) in claim 21, characterized by mixing one or more active ingredients according to any one of claims 21 to 40 with inert excipients in a manner known perse.

103. A process for the preparation of a pharmaceutical composition comprising a compound of the General Formula (III) in claim 41 , characterized by mixing one or more active ingredients according to any one of claims 41 to 60 with inert excipients in a manner known per se.

About IPPF

The International Pemphigus & Pemphigoid Foundation’s most important objectives are to provide patients and doctors worldwide with information about pemphigus and pemphigoid, and to provide patients and their caregivers much needed comfort and support so they can continue to live active, productive lives.Read more »